Expression of p16 induces transcriptional downregulation of the RB gene.
The RB and p16(INK4A) tumor suppressor genes function in the same pathway of cell cycle control. Previous evidence indicates that the p16(INK4A) gene is transcriptionally repressed by the RB gene product, pRB. In this study using human ovarian cancer cell lines, we found that RB protein and mRNA were expressed at higher levels in cell lines lacking p16 than in those with normal p16. Since this suggests a potential role of p16 in regulating the cellular level of pRB, we studied the effect of wild-type p16(INK4A) on expression of the RB gene. Introduction of p16(INK4A), carried by an adenovirus vector, into p16-negative cell lines dramatically decreased expression of RB protein and mRNA. Nuclei run-off assays demonstrated that p16 expression induced transcriptional downregulation of the RB gene. These results indicate that expression of RB is inversely regulated by p16. The findings reveal a new dimension of pRB-p16 interaction and should have implications for p16(INK4A)-mediated gene therapy.
Fang
X
X
Department of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Jin
X
X
Xu
H J
HJ
Liu
L
L
Peng
H Q
HQ
Hogg
D
D
Roth
J A
JA
Yu
Y
Y
Xu
F
F
Bast
R C
RC
Mills
G B
GB
D000256:Adenoviridae / Q000235:genetics; D002352:Carrier Proteins; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000235:genetics*; D050684:E2F Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D005822:Genetic Vectors; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors